Lu M, Conzen S D, Cole C N, Arrick B A
Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Cancer Res. 1996 Oct 15;56(20):4578-81.
BRCA1 has been identified as a tumor suppressor gene that is mutated in many cases of inherited breast and ovarian cancer. Recent data suggest that multiple splice forms of BRCA1 exist, but the structure and function of these alternative transcripts have not been elucidated. By sequence analysis of reverse transcription-PCR products, we have determined that a major splice form of BRCA1 expressed in malignant and nonmalignant breast epithelial cells contains an in-frame deletion of 3309 nucleotides from exon 11. A second alternative splice event results in the in-frame deletion of the 123 nucleotides that make up exons 9 and 10. These splice variants are found on polysomes and are therefore predicted to encode 80-85-kDa BRCA1-derived proteins lacking approximately 60% of the internal amino acids that constitute full-length BRCA1.
BRCA1已被鉴定为一种肿瘤抑制基因，在许多遗传性乳腺癌和卵巢癌病例中发生突变。最近的数据表明BRCA1存在多种剪接形式，但这些可变转录本的结构和功能尚未阐明。通过对逆转录-聚合酶链反应（RT-PCR）产物进行序列分析，我们确定在恶性和非恶性乳腺上皮细胞中表达的BRCA1的一种主要剪接形式包含外显子11中3309个核苷酸的框内缺失。第二个可变剪接事件导致构成外显子9和10的123个核苷酸的框内缺失。这些剪接变体存在于多核糖体上，因此预计可编码80-85 kDa的BRCA1衍生蛋白，这些蛋白缺少构成全长BRCA1的约60%的内部氨基酸。
